The overall aim of this proposal is to understand the specific functions of the primary (SI) and secondary (SII) somatosensory cortices and the thalamus in the representation of sensory aspects of pain. Although the important roles of SI, SII, and thalamus in the representation of the location, intensity, and modality of pain have long been recognized, their specific functions and the underlying anatomical and neural basis have not yet been established. Our limited knowledge of the fine-scale functional organization of the nociceptive system and of the electrophysiological properties of nociceptive neurons has become a major obstacle to a complete understanding of the mechanisms underlying the phenomenon of pain. To address these issues, we propose to use a multi-model approach including submillimeter fMRI, unit electrophysiology, and histology in anesthetized monkeys to identify nociceptive regions and quantitatively characterize their response properties to noxious and innocuous thermal and mechanical stimuli, to examine the electrophysiological properties of nociceptive neurons, and to establish their functional and anatomical connections. By taking advantages of the high signal to noise ratio at 9.4 T, we propose to use the functional connectivity measure to probe the functional hierarchical relationship among nociceptive regions. There are three specific aims. Aim 1 proposes to determine the cortical representation of nociception in SI and SII cortices. Aim 2 proposes to examine the representation of nociception in thalamus.. Aim 3 proposes to determine the functional and anatomical connectivity of nociceptive regions in SI, SII and thalamus. At the completion of this study, we will have a better understanding about the functional and anatomical organization of the nociceptive system in SI, SII, and thalamus and the electrophysiological basis for nociceptive processing. This knowledge is crucial for understanding the neural mechanisms of pain and ultimately will provide a crucial link between the perception of pain and its underlying neural mechanisms and anatomical framework. PUBLIC HEALTH RELEVANCE: This study centers on understanding where and how the sensory aspects of pain perception such as the location (where), intensity (how strong), and quality of pain are encoded in the brain. A more complete understanding of the flowchart of painful information processing in the thalamocortical circutry would promote new therapeutic ideas, which will lead to more rational and reliable treatments for chronic pain.